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Abstract
Fbh1 (F-box DNA helicase 1) orthologues are conserved from Schizosaccharomyces pombe to chickens and humans. Here, we report the disruption of the FBH1 gene in DT40 cells. Although the yeast fbh1 mutant shows an increase in sensitivity to DNA damaging agents, FBH1−/− DT40 clones show no prominent sensitivity, suggesting that the loss of FBH1 might be compensated by other genes. However, FBH1−/− cells exhibit increases in both sister chromatid exchange and the formation of radial structures between homologous chromosomes without showing a defect in homologous recombination. This phenotype is reminiscent of BLM−/− cells and suggests that Fbh1 may be involved in preventing extensive strand exchange during homologous recombination. In addition, disruption of RAD54, a major homologous recombination factor in FBH1−/− cells, results in a marked increase in chromosome-type breaks (breaks on both sister chromatids at the same place) following replication fork arrest. Further, FBH1BLM cells showed additive increases in both sister chromatid exchange and the formation of radial chromosomes. These data suggest that Fbh1 acts in parallel with Bloom helicase to control recombination-mediated double-strand-break repair at replication blocks and to reduce the frequency of crossover.
SUPPLEMENTAL MATERIAL
We thank the members of the Takeda laboratories for help and support. Special thanks go to Y. Sato, M. Nakaoka, and R. Ohta for technical assistance. We also thank M. Seki (Tohoku University) for helpful discussions and M. C. Whitby (University of Oxford) for critical reading and discussion.
Financial support was provided in part by a grant from Core Research for Evolutional Science and Technology (CREST) of Japan Science and Technology Corporation; by a Center of Excellence (COE) grant to S.T.; by a Grant-In-Aid for Priority Areas to H.S. for Scientific Research from the Ministry of Education, Culture, Sports, Science and Technology of Japan; and by grants from The Uehara Memorial Foundation and The Naito Foundation.